CRCNS: Dynamics and mechanisms of rhythmic activity in basal ganglia

CRCNS：基底节节律活动的动力学和机制

• 批准号: 7777622
• 负责人: LEONID L RUBCHINSKY
• 金额: $ 24.23万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7777622
• 关键词: Basal Ganglia; Basal Ganglia Diseases; Behavior; Biological; Birth; Brain; Cell Nucleus; Cells; Chronic; Clinical; Computer Simulation; Data Analyses; Deep Brain Stimulation; Detection; Development; Disease; Dopamine; Exhibits; Goals; Human; Language; Methods; Modeling; Movement; Neurodegenerative Disorders; Parkinson Disease; Patients; Pattern; Periodicity; Physiological; Physiology; Play; Role; Scheme; Study Subject; Symptoms; Synapses; System; Thalamic structure; base; improved; in vivo; interest; motor control; motor deficit; neuroregulation; public health relevance; research study; tool

DESCRIPTION (provided by applicant): The basal ganglia (BG) are a group of subcortical nuclei receiving extensive projections from cortex and sending extensive projections to thalamus and which are, among other things, involved in neural control of movement. Interest in BG physiology is also motivated by BG-related disorders, especially Parkinson's disease (PD) - a major neurodegenerative disorder characterized by chronic dopamine (DA) deficiency resulting in a set of primarily movement-related symptoms. Although BG plays a significant role in motor control and in motor deficits of PD, the physiological mechanisms responsible for this control and for PD motor deficits remain poorly understood. Recent studies indicate that patterns of oscillatory synchronous activity in BG, although very variable, are strongly relevant to BG physiology and BG disorders, such as PD. The dynamics of these oscillations and their mechanisms are the subjects of this study. Patterns of synchronous oscillatory behavior in spiking units and local field potentials (LFP) will be recorded from BG of human patients and analyzed using a method of synchronous episodes detection. Models, which are adequately constrained by the results of analysis of the variable patterns of synchronous activity recorded from the patients, will be developed. This model will be used as a tool to investigate the mechanisms responsible for the origin of intermittent synchronous behavior and thus identify possible mechanisms in vivo. Bifurcations underlying the occurrence of physiologically realistic dynamics in numerical experiments with the full model and in an analytical approach to a reduced system will be studies. As a result, the mechanisms of the intermittent synchronous activity in BG both in the "biological language" (features of synapses, cells, and connectivity, which give birth to intermittent synchrony) and in "mathematical language" (bifurcations in the system, exhibiting realistic rhythmicity) will be understood. Based on the understanding of the mechanisms, potential methods for modulation and suppression of this rhythmicity (which is believed to be pathological) will be suggested. PUBLIC HEALTH RELEVANCE: The project will enhance understanding of physiology of human brain in Parkinson's disease, a major neurodegenerative disorder. The results of the project may assist in development of new therapies for this disease and related disorders.

描述（由申请人提供）：基底神经节（BG）是一组皮质下核，接收来自皮质的广泛投射并向丘脑发送广泛投射，除其他外，其参与运动的神经控制。对 BG 生理学的兴趣也源于 BG 相关疾病，尤其是帕金森病 (PD)，这是一种主要的神经退行性疾病，其特征是慢性多巴胺 (DA) 缺乏，导致一系列主要与运动相关的症状。尽管 BG 在 PD 的运动控制和运动缺陷中发挥着重要作用，但负责这种控制和 PD 运动缺陷的生理机制仍知之甚少。最近的研究表明，BG 振荡同步活动的模式虽然变化很大，但与 BG 生理学和 BG 疾病（例如 PD）密切相关。 这些振荡的动力学及其机制是本研究的主题。将从人类患者的 BG 中记录尖峰单元和局部场电位 (LFP) 的同步振荡行为模式，并使用同步发作检测方法进行分析。将开发由患者记录的同步活动的可变模式的分析结果充分约束的模型。该模型将用作研究间歇性同步行为起源机制的工具，从而识别体内可能的机制。将研究完整模型的数值实验和简化系统的分析方法中生理学真实动力学发生的分岔。因此，BG 间歇性同步活动的机制将在“生物语言”（突触、细胞和连通性的特征，产生间歇性同步）和“数学语言”（系统中的分叉，表现出现实的节律性）方面得到理解。基于对机制的理解，将提出调节和抑制这种节律性（被认为是病理性的）的潜在方法。公共健康相关性：该项目将增进对帕金森病（一种主要神经退行性疾病）中人脑生理学的了解。该项目的结果可能有助于开发针对这种疾病和相关疾病的新疗法。